Pregnancy: Corpus luteum failure in ectopic pregnancy

The endocrinology of ectopic pregnancy was studied in orderto investigate the origin of the discordance in the circulatingamounts of human chorionic gonadotrophin (HCG) and those ofoestradiol and progesterone. Serial maternal blood samples wereobtained at 4–9 weeks gestation from 93 patients who becamepregnant following in-vitro fertilization and embryo transferincluding 10 ectopic, 21 anembryonic and 62 normal singletonpregnancies. The samples were analysed for HCG, Schwangerschaftprotein-1 (SP-1), pregnancy-associated plasma protein-A (PAPP-A),progesterone and oestradiol. In ectopic pregnancies, concentrationsof all substances analysed were significantly reduced comparedto singleton pregnancies from 5 weeks gestation (P < 0.05–0.001)but they were not significantly different from those of anembryonicpregnancies. In ectopic pregnancies, associations were foundbetween the concentration of both HCG and SP-1 and those ofprogesterone and oestradiol. No associations were found betweenPAPP-A and any other substances analysed. This may be due toinsensitivity of the PAPP-A assay; alternatively PAPP-A concentrationsmay be differentially reduced in ectopic pregnancy. These findingssuggest that progesterone and oestradiol are derived from thecorpus luteum in early ectopic pregnancy but that the corpusluteum fails rapidly and the dominant source of both hormonesbecomes the trophoblast as early as 5 weeks.     

Pregnancy: Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight

Serum concentrations of human chorionic gonadotrophin (HCG),Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasmaprotein A (PAPP-A), progesterone and oestradiol were measuredat weekly intervals between the fifth (embryo transfer plus3 weeks) and 13th week of gestation during the first trimesterof pregnancies achieved following in-vitro fertilization (IVF)and embryo transfer in a group of women who delivered before(n = 8) or at term (n = 52). Those women who had a preterm deliveryhad significantly lower concentrations of PAPP-A (weeks 7–13;P = 0.0001–0.028) and SP-1 (weeks 6–8 and 10–12;P = 0.004–0.04). After correction of birth weight forsex and gestational age at delivery, preterm delivery was foundnot to be associated with growth retardation. However, comparisonof the circulating concentrations of the substances analysedin mothers who delivered babies of < 85% of the 50th centileof the normal range of birth weight for a given gestationalage and sex, with those who delivered babies of >85% revealedthat the concentrations of HCG (P = 0.012–0.04 on weeks6–9) and SP-1 (P = 0.003–0.03 on weeks 7, 9–13)were significantly lower in the former group. Weak, inconsistentassociations were found between the circulating concentrationsof HCG, SP-1 and PAPP-A and both corrected birth weight andgestational age at delivery. Thus, both the gestational ageat delivery and low birth weight may be related to impairedplacental development/function during the first trimester.     

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest(‘blighted ovum’) (n = 9) were studied 16 days afterconception, at a time when they were asymptomatic and serumconcentrations of -human chorionic gonadotrophin (HCG) werein the normal range and increasing at an apparently normal rate.Serum progesterone and oestradiol concentrations were comparedwith those from normal women matched for gestational age andserum -HCG concentration whose singleton intra-uterine pregnanciesproceeded normally beyond 20 weeks. Mean serum progesteroneconcentrations were significantly lower in the women with ectopicpregnancies than in matched controls (P < 0.002); however,there was no difference in the serum progesterone concentrationsbetween women with blighted ova and matched controls. Statisticallysignificant differences were not seen in serum oestradiol concentrationsbetween either group and matched controls. Similarly there wasno difference in serum progesterone or oestradiol concentrationsin 20 women who conceived ectopic pregnancies and 20 women conceivingblighted ovum pregnancies and their matched intra-uterine controlswhen conception followed ovarian stimulation. The low serumprogesterone concentrations seen in ectopic pregnancy suggestthat there is a specific and selective deficiency in progesteronesynthesis, which implies that factors other than HCG may influenceluteal function.     

Relationship of biochemical pregnancy to pre-ovulatory endometrial thickness and pattern in patients undergoing ovulation induction

In order to assess the relationship between pre-ovulatory endometrialthickness and pattern and biochemical pregnancy, the pregnancyoutcome was retrospectively analysed in 81 patients undergoingovulation induction evaluated by vaginal ultrasound on the dayof human chorionic gonadotrophin (HCG) administration or luteinizinghormone (LH) surge. Biochemical pregnancies occurred in 7/32(21.9%) pregnancies when endometrial thickness was <9 mm,compared to 0/49 when endometrial thickness was 9 mm on theday of HCG administration or LH surge (P < 0.0025). Clinicalabortions occurred in 5/32 (15.6%) pregnancies when endometrialthickness was 6–8 mm, compared to 6/49 (12.2%) when endometrialthickness was 6–8 mm (NS). Endometrial thickness was relatedto the cycle day of HCG or LH surge (r = 0.37, P < 0.001)but was unrelated to oestradiol level on the day of HCG administrationor LH surge (r = 0.12). Biochemical pregnancies were relatedto endometrial pattern (r = – 0.22, P = 0.02) but wereunrelated to maternal age or previous abortions. Clinical abortionswere related to age (r = 0.26, P = 0.01) and to previous abortion(r = 0.25, P = 0.013) but were unrelated to endometrial pattern.Neither biochemical pregnancy nor clinical abortion was relatedto oestradiol or LH levels on the day of HCG administrationor LH surge. These findings suggest that the majority of biochemicalpregnancies do not result from karyotypically abnormal embryos,as do clinical abortions.     

Triggering of ovulation in human menopausal gonadotrophin-stimulated cycles: comparison between intravenously administered gonadotrophin-releasing hormone (100 and 500 {micro}g), GnRH agonist (buserelin, 500 {micro}g) and human chorionic gonadotrophin (10 000 IU)

We studied the peri-ovulatory and luteal phases in 38 humanmenopausal gonadotrophin (HMG)-stimulated cycles, in which ovulationwas triggered with four different i.v. bolus ovulation triggers:100 µg gonadotrophin-releasing hormone (GnRH; group A,n = 9), 500 µg GnRH agonist (GnRHa; group B, n = 10),10 000IU human chorionic gonadotrophin (HCG; group C, n = 10)and 500 µg GnRH (group D, n = 9). Endogenous luteinizinghormone (LH) surges occurred in all cycles of groups A, B andD. The rise was slowest but highest in group B (P < 0.0001)and lowest in group A. Although the t₀ serum oestradiol valueswere similar in all groups, day +8 oestradiol and day +4 and+8 progesterone concentrations were higher in group C (P <0.05). At day +4 and +8, serum LH concentrations were lowest(P < 0.01) but follicle stimulating hormone (FSH) concentrationswere higher. Clinically, day +8 luteal scores showed a moreconspicuous degree of ovarian hyperstimulation in the HCG group(P = 0.0292). Luteal insufficiency, defined as cycles with progesteroneconcentrations of <8 ng/ml, occurred much more frequentlyin groups A, B and D than in group C (day +4: P < 0.0003;day +8: P < 0.0001), despite progesterone supplementation.Three pregnancies (one in group C and two in group D) and onemoderate case of ovarian hyperstimulation syndrome (OHSS) (ina non-conceptional group D cycle) occurred. These findings showthat (i) ovulation occurs and pregnancy can be achieved followingan endogenous LH surge induced by GnRH and its agonists, (ii)a high frequency of luteal insufficiency occurs in such cycleseven with luteal supplementation and (iii) OHSS cannot be totallyprevented by this approach, although cycles with an endogenousLH surge in general result in fewer subclinical signs of ovarianhyperstimulation.     

Melatonin and steroids in human pre-ovulatory follicular fluid: seasonal variations and granulosa cell steroid production

Follicular fluid samples were obtained from the largest pre-ovulatoryfollicle of 120 women undergoing in-vitro fertilization andwere examined for melatonin by enzyme-linked immunosorbent assayand the steroids oestradiol and progesterone by radioimmunoassay.The concentrations (mean ± SE) of melatonin (213.4 ±18.9 pmol/1) and progesterone (20.1 ± 1.1 µmol/l)in follicular fluid during the autumn and winter (dark) monthswere significantly higher than during the spring and summer(light) months, melatonin (138.4 ± 12.5 pmol/1) and progesterone(11.6 ± 0.8 µmol/l). By contrast, oestradiol concentrationswere significantly lower during the dark months than duringthe light months (264.7 ± 44.1 and 661.8 ± 55.1nmol/l respectively). There was a positive correlation betweenfollicular fluid melatonin and progesterone concentrations (r= 0.271, P < 0.05, n = 120) and a negative relationship betweenmelatonin and oestradiol (r = –0.254, P < 0.05, n =120). The effects of melatonin alone and in combination withhuman chorionic gonadotrophin (HCG) or follicle stimulatinghormone (FSH) on steroidogenesis by human granulosa cell culturewere also investigated. Melatonin had minimal effects on oestradiolor progesterone production by granulosa cells. Interestingly,the oestradiol response in culture appeared to be differentaccording to the time of the year when harvested. During thelight period oestradiol production was enhanced. Melatonin alsosynergized with HCG in increasing progesterone production ondays 6 and 7 after treatment during both light and dark periods.FSH stimulated oestradiol production by the cells on day 2 ofculture. Melatonin had no effect on FSH stimulation of oestradiolproduction. The results of this study suggest that melatoninmay be involved in the regulation of steroidogenesis by thehuman ovaries.     

Protein and steroid levels in embryonic cavities in early human pregnancy

Biochemical analysis including concentrations of urea, creatinine,human chorionic gonadotrophin (HCG), oestradiol, progesterone,and -fetoprotein (AFP), twodimensional gel electrophoresis,and the affinity of AFP for Concanavalin A (Con A)—Sepharosewere performed on samples of exocoelomic and amniotic fluidsretrieved by transvaginal puncture and maternal serum from 25normal pregnancies between 5 and 12 weeks of gestation. Biochemicalassays showed that during this period of gestation no differencesin urea concentration were found between fluids from the threecompartments, whereas creatinine concentration decreased significantly(P < 0.001) from maternal serum to amniotic fluid. The exocoelomicfluid contained significantly (P < 0.001) higher concentrationsof oestradiol, progesterone and HCG than both maternal serumand amniotic fluid. AFP concentration was similar in amnioticand exocoelomic fluids and significantly (P < 0.001) lowerin maternal serum. Between the second and the third months ofgestation, urea concentration decreased significantly (P <0.05) and oestradiol, HCG and AFP increased significantly inmaternal serum (P < 0.05, P < 0.05, P < 0.001, respectively).During the same period of gestation, exocoelomic fluid concentrationsof urea and HCG decreased significantly (P < 0.005, P <0.001, respectively). Comparison of the two-dimensional gelpatterns obtained from maternal serum with those from exocoelomicamniotic fluids revealed no significant qualitative differences,except for several small proteins. These results suggest thatprotein pathways across materno-embryonic membranes are notsimply passive transfers. Con A affinity molecular variantsof AFP demonstrated that both exocoelomic and amniotic fluidAFP were mainly of yolk sac origin and that maternal serum AFPwas mainly of fetal liver origin, suggesting that the humansecondary yolk sac has both absorptive and excretory functions.     

Endocrinology: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial

Two different regimens of luteal support in gonadotrophin hormone-releasinghormone (GnRH) analoguefhuman menopausal gonadotrophin (GnRHa/HMG)-inducedin-vitro fertilization cycles (IVF) were compared in a randomizedclinical trial. After embryo transfer, either vaginal progesteronealone was administered (n=89, P group), or a combination ofvaginal progesterone and human chorionic gonadotrophin (n=87,P/HCG group). The primary aim of this study was to assess theeffect of the different regimens of luteal support on the pregnancyrate. The secondary aim was to compare oestradiol and progesteroneconcentrations in the luteal phase between the two groups, andassess their effect on the pregnancy rate. A clinical pregnancyrate of 15% was found in the P/HCG group in comparison with26% in the P group (odds ratio 0.49; 99% confidence interval:0.18–1.3). The luteal serum oestradiol and progesteronevalues in the P/HCG group were significantly higher when comparedwith the P group on the 6th, 9th and 12th day after oocyte retrieval(Wilcoxon P<0.001). In accordance with the high oestradiolconcentrations, more cases of ovarian hyperstimulation syndrome(OHSS) were found in the P/HCG group. Oestradiol values on the9th day after oocyte retrieval, presumably the day of implantation,appeared to be higher in women who did not become clinicallypregnant. We conclude that vaginal progesterone alone providessufficient luteal support in GnRHa/HMG induced IVF cycles. Thecombination of vaginal progesterone and HCG as luteal supportleads to significant high luteal oestradiol and progesteroneconcentrations. But a high concentration of oestradiol seemsto have a deleterious effect on the implantation process, resultingin a low pregnancy rate.     

Endocirnology: Comparison between prolactin, gonadotrophins and steroid hormones in serum and follicular fluid after stimulation with gonadotrophin-releasing hormone agonists and human menopausal gonadotrophin for an in-vitro fertilization programme

The inter-relationship between serum and follicular fluid prolactin,oestradiol, progesterone, follicle stimulating hormone (FSH),and luteinizing hormone (LH) in two groups of women was investigated.In group 1, 32 women were treated with gonadotrophin-releasinghormone agonist (GnRH-a) in a long term protocol and subsequentlystimulated with human menopausal gonadotrophin (HMG). In group2, 25 women were simultaneously stimulated with GnRH-a in ashort protocol with HMG. Follicular fluid was collected from54 follicles in group 1 and 47 follicles in group 2. Serum wasobtained on the day of human chorionic gonadotrophin (HCG) administration.Serum prolactin and oestradiol concentrations were significantlyhigher (P < 0.025 and P< 0.01, respectively) in group1 than in group 2. Serum LH (P < 0.005), FSH (P< 0.01)and progesterone (P < 0.025) were significantly lower ingroup 1 than in group 2. Follicular fluid prolactin was significantlyhigher (P < 0.005) in group 1. No differences were foundin follicular fluid progesterone and oestradiol. Follicularfluid LH was significantly lower (P < 0.005) in group 1.Serum prolactin correlated positively with oestradiol in bothgroups (P < 0.005 group 1; P < 0.02 group 2). No significantcorrelation was found between serum prolactin and LH in group1. We conclude that prolactin secretion is independent fromLH secretion. Hyperprolactinaemia, which is observed in womenstimulated with GnRH-a and HMG, is positively associated withincreased oestradiol.     

Endocrinology of in-vitro fertilization pregnancies during the first trimester

The endocrine function of the corpus luteum and placenta andthe inter-relationships between ovarian steroids and the placentalproteins in pregnancies achieved following ovarian stimulation,in-vitro fertilization and embryo transfer (IVF-ET) have beeninvestigated. The serum concentrations of human chorionic gonadotrophin(HCG), Schwangerschaft protein-1 (SP-1), pregnancy-associatedplasma protein A (PAPP-A), progesterone and oestradiol weremeasured at weekly intervals between the 4th (ET plus 2 weeks)and 14th week of gestation in 86 pregnancies. The mean concentrationsof the placental proteins and oestradiol were significantlyhigher in twin than in singleton pregnancies from as early as5 weeks gestation, but the mean concentrations of progesteronewere significantly higher only at the end of the first trimester.Ranking, as demonstrated by the presence of statistically significantcorrelations between serum levels of each substance analysedin week 13 with those of preceding weeks, was established forprogesterone and SP-1 from the 5th week, for oestradiol andPAPP-A from the 7th week and for HCG from the 8th week of gestation.The presence of statistically significant correlations betweeneach substance analysed suggests that the placenta becomes thedominant source of oestradiol from 8 weeks gestation and ofprogesterone not until 12 weeks gestation, and that the placentalsynthesis of HCG, SP-1, PAPP-A, oestradiol and progesteroneappear to be linked. There were no statistically significantcorrelations between the serum concentrations of HCG and eitherprogesterone or oestradiol until the production of each hadbecome predominantly placental.     

Pregnancy: Temporal relationship between the human chorionic gonadotrophin peak and the establishment of intervillous blood flow in early pregnancy

The purpose of this study was to investigate the temporal relationshipbetween the early pregnancy peak of circulating human chorionicgonadotrophin (HCG) concentration and the establishment of maternalblood flow in the placental intervillous space. The presenceof blood flow echoes within intervillous space was determinedby colour Doppler imaging from 44 women with clinically uncomplicatedpregnancy between 6 and 18 weeks gestation. Circulating HCG,free - and HCG subunits, oestradiol and progesterone concentrationswere immunoassayed in blood samples collected at the time ofDoppler examination. A continuous intervillous blood flow wasdetected in all cases with a gestational age 11.7 weeks (n =18) but never before this time. Circulating concentrations offree HCG, oestradiol and progesterone were linearly or exponentiallycorrelated with gestational age (r = 0.860, 0.903 and 0.538respectively, all with P < 0.001), indicating steady increaseof these hormones with advancing gestation. However, the bestfitted lines were found to be parabolic for HCG (r = 0.771,P < 0.001) and HCG (r = 0.695, P < 0.001), their highestpoints corresponding to 11.24 and 10.74 weeks gestational agerespectively. The close temporal relationship between the Doppleradvent of intervillous maternal blood flow and the HCG peaksuggests that the establishment of the intervillous blood flowis associated with the decline in circulating HCG concentrations.     

Atrial natriuretic peptide, oestradiol and progesterone in women undergoing spontaneous and gonadotrophin-stimulated ovulatory cycles

The objective of this study was to examine the relationshipbetween the concentrations of oestradiol and progesterone onthe one hand and atrial natriuretic peptide (ANP) concentrationson the other, during the follicular and luteal phases of spontaneousand gonadotrophin-stimulated ovulatory menstrual cycles. A totalof 27 ovulatory women undergoing either a spontaneous (n = 9)or a gonadotrophin-stimulated (n = 18) cycle were selected forinclusion in this study. In comparison with spontaneous cycles,gonadotrophin-stimulated cycles had increased peak follicularoestradiol (mean ± SE; 937 ± 150 versus 195 ±18 pg/ml; P < 0.05) and midluteal progesterone (mean ± SE; 44.0 ± 7.4 versus 14.1 ± 2.4 ng/ml; P <0.05) concentrations. There were no differences in the circulatingANP concentrations between the follicular and luteal phasesof the menstrual cycle. Despite the increased oestradiol andprogesterone concentrations following gonadotrophin stimulation,no difference in ANP concentrations was seen between stimulatedand spontaneous cycles. There was no correlation between circulatingconcentrations of oestradiol, progesterone (at physiologicaland supraphysiological concentrations) and ANP throughout themenstrual cycle.     

Steroid Production by the cumulus: relationship to fertilization in vitro

Insemination media were Collected from 92 follicles of 14 patientsstimulated to progesterone and oestradiol in the inseminationdrops were assayed, corrected for carry–over from follicularfluid and volume and expressed as production per µg ofprotein in the cumulus. significantly higher progesteron productionper unit protein was associated with oocytes which fertilizedin vitro (P << 0.02). Oocytes fertilizing with subsequentfragmentation or degeneration showed progesterone levels significantlyhigher than oocytes fertilizing normaly (P << 0.05). Polyspermicoocytes ( n = 3 ) were associated with very high levels of progesteroneproduction but were not significantiy different due to the lownumbers. Oestradial production per unit protein was significantlygreater in oocytes which degenerated (P << 0.05). TheProtein content of cumuli whose oocytes fertilized appearedto be significantly lower than those which did not (P <<0.05). these results probably reflect the maturity of the folliclealthough direct actions of cumulus products upon gametes cannotbe ruled out.     

Endocrinology: Daily measurements and in-vitro effects of human chorionic gonadotrophin in the early luteal phase

The purpose of the present study was to analyse daily measurementsof human chorionic gonadotrophin (HCG) in in-vitro fertilization(IVF) cycles and to reproduce the effects of HCG in vitro usinghuman granulosa—luteinized cells from the same patients.The study population consisted of nine women undergoing IVFbecause of tubal infertility in whom blood was drawn every 24h from the day of the ovulatory dose of HCG (10 000 IU) until6 days after ovum pick-up. Granulosa—luteal cells fromthe follicular aspirates were collected and cultured in vitroup to 6 days in the presence of increasing concentrations (0,0.01, 0.1, 1.0 and 100.0 IU/ml) of HCG. Serum progesterone andHCG in vivo as well as progesterone accumulation in vitro ondays 2, 4 and 6, were the main outcome measures. Maximum HCGconcentrations (0.25 IU/ml) were reached the day before ovumpick-up, and continuously decreased until day 6 after ovum retrieval.HCG did not stimulate progesterone production in vitro at anydose tested until day 6 after ovum pick-up. Then, 0.01 IU/mlresulted significantly (P < 0.05) stimulatory compared tocontrols, while 1.0 IU/ml was inhibitory (P < 0.05). It isconcluded that HCG supplementation in an IVF cycle is unnecessaryuntil day 6 after ovum pick-up. On day 6, progesterone productionis stimulated with very low concentrations of HCG.     

Pregnancy: The expectant management of early pregnancies of uncertain site

The role of expectant management was evaluated in 80 women inwhom clinical examination, including vaginal ultrasound, hadfailed to identify the location of an early pregnancy. In 45cases, spontaneous resolution of the pregnancy products occurred.A normal intra-uterine pregnancy was diagnosed in 12 patients.A total of 23 patients underwent active therapeutic measuresdue to an ectopic pregnancy (n = 16) or a spontaneous abortion(n = 7). The effectiveness of different diagnostic measuresto identify patients suitable for expectant management was analysed.In 33/34 patients (97%) with a relative daily human chorionicgonadotrophin (HCG) change of <–5%, and a serum progesteroneconcentration of <20 nmol/l, spontaneous resolution of thepregnancy products occurred. Among 46 cases, with a relativedaily HCG change of >–5% and/or serum progesterone>20 nmol/l, active therapeutic measures were carried outin 22 cases (48%), a normal intra-uterine pregnancy was diagnosedin 12 cases (26%) and spontaneous resolution of the pregnancyproducts occurred in 12 cases (26%). In conclusion, the combinationof a single progesterone assay and serial HCG determinationsretrospectively identified early pregnancies of uncertain locationin whom expectant management was a safe management option.     

Pregnancy: Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advancedreproductive age (45 years old) and followed their pregnanciesthrough to delivery in order to assess obstetrical outcomes.Patients (n = 162) aged 45–59 years (mean ± SD;47.3 ± 3.4 years) underwent 218 consecutive attemptsto achieve pregnancy. Oocytes (16.2 ± 7.2 per retrieval)were provided by donors 35 years old. Cleaving embryos (8.2± 4.8 zygotes/couple) were transferred trans-cervically(4.5 ± 1.1 per embryo transfer) to recipients prescribedoral micronized oestradiol and intramuscular progesterone. Followingoocyte aspiration there were six instances of non-fertilization(2.8%) and 212 embryo transfers. A total of 103 pregnancieswas established for an overall pregnancy rate (PR) of 48.6%,which included 17 preclinical pregnancies, 12 spontaneous abortions,and 74 delivered pregnancies (clinical PR 40.6%; delivered PR34.9%). Multiple gestations were frequent (n = 29; 39.2% ofpregnancies) and included 20 twins, seven triplets, and twoquadruplets. Two of the triplet and both of the quadruplet pregnanciesunderwent selective reduction to twins. Antenatal complicationsoccurred in 28 women (37.8% of deliveries) and included pretermlabour (n = 9), gestational hypertension (n = 8), gestationaldiabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia(n = 2), HELLP syndrome (n = 2), and fetal growth retardation(n = 2). 48 (64.8%) deliveries were by Caesa-rean section. Thegestational age at delivery for singletons was 383 ±1.3 weeks (range 35–41 weeks), with birth weight 3218± 513 g (range 1870–4775 g); twins 35.9 ±2.0 weeks (range 32–39 weeks), birth weight 2558 ±497 g (range 1700-3450 g); and triplets 33.5 ± 0.7 weeks(range 32-34 weeks), birth weight 1775 ± 190 g (range1550-2100 g). Neonatal complications (4.6% of babies born) includedgrowth retardation (n = 2), trisomy 21 (n = 1), ventricularseptal defect (n = 1), and small bowel obstruction (n = 1).There were no maternal or neonatal deaths. We conclude thatoocyte donation to women of advanced reproductive age is highlysuccessful in establishing pregnancy. However, despite carefulantenatal screening, obstetrical complications are common, oftensecondary to multiple gestation.     

A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation

A prospective randomized study was conducted to evaluate theuse of adding oestradiol valerate 6 mg per os daily to intravaginalmicronized progesterone (600 mg daily) as luteal supplements.The study comprised 378 infertile women superovulated with agonadotrophin releasing-hormone agonist (GnRHa) and human menopausalgonadotrophins (HMG) for in-vitro fertilization (IVF) or zygoteintra-Fallopian transfer (ZIFT). The clinical pregnancy ratewas similar (29%) whether or not oestradiol valerate was addedto intravaginal progesterone. Eighteen out of twenty-two endometrialbiopsies were in phase, and morphological evaluations of thetwo luteal supplementation groups were not different. Serumhormone profiles in singleton pregnancies showed a similar dayof appearance of human chorionic gonadotrophin (HCG) in bothprotocols but significantly lower oestradiol concentrationsarose in the group without oestradiol valerate. In 32% of thesingleton pregnancies, the first appearance of HCG occurredlater than day 12 after HCG injection; in those ongoing pregnancies,corpus luteum rescue—as measured by significantly lowerserum oestradiol and progesterone concentrations—was compromised.This study provided no evidence of any benefit of routinelysupplementing GnRHa/HMG cycles with oestradiol valerate in additionto intravaginal micronized progesterone.     

Endocrinology: Luteal function following ovulation induction in polycystic ovary syndrome patients using exogenous gonadotrophins in combination with a gonadotrophin-releasing hormone agonist

The luteal phase was studied in 12 polycystic ovary syndrome(PCOS) patients following ovulation induction using exogenousgonadotrophins combined with a gonadotrophin-releasing hormoneagonist (GnRH-a). Human menopausal gonadotrophin (HMG) was precededby 3 weeks of treatment with GnRH-a (buserelin; 1200 µg/dayintra-nasally) and administered in a step-down dose regimenstarting with 225 IU/day i.m. GnRH-a was withheld the day beforeadministration of human chorionic gonadotrophin (HCG; 10 000IU i.m.). Blood sampling and ultrasound monitoring was performedevery 2–3 days until menses. The luteal phase was significantlyshorter in PCOS patients as compared to eight regularly cyclingcontrols: 8.8 (3.3–11.4) days [median(range)] versus 12.8(8.9–15.9) days (P = 0.01). Median peak values for progesteronedid not show significant differences comparing both groups:52.3 (17.1–510.3) nmol/l versus 43.0 (31.2–71.1)nmol/l, respectively (P = 0.8). The interval between the dayof the progesterone peak and return to baseline was significantlyshorter in the PCOS patients than in controls: 2.5 (0.3–4.9)days versus 4.2 (3.9–10.5) days (P < 0.005). Luteinizinghormone (LH) concentrations during the luteal phase as reflectedby area under the curve were significantly lower in PCOS ascompared to controls: 4.4 (1.6–21.0) IU/l x days and 49.0(27.8–79.6) IU/l x days, respectively (P < 0.001).In conclusion, patients with PCOS may suffer from insufficientluteal phases after ovulation induction using HMG/HCG in combinationwith a GnRH-a. The corpus luteum apparently lacks the supportof endogenous LH and may be stimulated only by the pre-ovulatoryinjection of HCG. Potential involvement of adjuvant GnRH-a medicationor HCG itself in luteal suppression of endogenous gonadotrophinsecretion, and the importance of luteal function for pregnancyrates following treatment, warrant further studies.     

Serum luteinzing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal fofficle stimulating hormone serum concentrations

The purpose of the study was to evaluate pulsatile luteinizinghormone (L release and intratesticular concentrations of testosteroneand oestradlol in infertile men, to determine if alterationsin gonadotrophin secretion are associated with changes in thetesticular concentrations of steroids. Patients with idiopathicoligo/azoospermia were divided into a high follicle stimulatinghormone (FSH) group (n=5) and a normal FSH group (n = 6). Bloodsamples were taken every 15 mm for 6 h to determine LH, FSH,testosterone, oestradiol, sex hormone binding globulin, bioactiveLH and bioavailable testosterone. The patients underwent a bilateraltesticular biopsy for histological assessment and to determinetestosterone and oestradiol concentrations. Serum measure mentswere compared with those of seven fertile men. The high FSHgroup had a higher concentration of serum UI and oestradiolthan normal men (P < 0.01) and showed a lower frequency ofLII pulses than the normal FSH group and control men (P <0.01). Intratesticular oestradiol was higher in the high FSHgroup (P < 0.001), with a lower testosterone/oestradlol ratio(P < 0.01). Patients showed a negative correlation betweenthe serum testosterone/LH ratio and FSH (r = -–0.75; P< 0.01) and a positive correlation between the testicularoestradiol concentration and serum FSH (r=0.86; P<0.01).The histopathological examination only showed a smaller tubediameter in the high FSll group (P < 0.05). These data seemto indicate that a higher intratesticular concentration of oestradiolwith a lower testosterone/oestradiol ratio in the high FSH groupcould have a deleterious effect on spermatogenesis.     

Endocrinology: Growth hormone, oestradiol, progesterone and testosterone concentrations in follicular fluid after ovarian stimulation with various regimes for assisted reproduction

Follicular fluid samples and oocytes were obtained from 75 women(87 cycles), who participated in an assisted conception programme.Determinations of the concentration of oestradiol, progesterone,testosterone and growth hormone were performed in all follicularfluid samples. Patients were stimulated with the following regimes:group A (24 cycles, 94 samples), human menopausal gonadotrophin(HMG) (three ampoules/day) and human chorionic gonadotrophin(HCG); group B (23 cycles, 53 samples), HMG/HCG with prednisolone(7.5 mg/day) after cycle programming with oral contraceptives;group C (40 cycles, 60 samples), buserelin with HMG/HCG. Oestradiolconcentrations (mean ± SEM) were significantly higher(P < 0.05) in group A (320.1 ± 27.3 ng/ ml) and thoseof growth hormone in both groups A and C (3.8 ± 0.2 and3.2 ± 0.15 ng/ml, respectively), as compared to the othergroups, whereas progesterone and testosterone concentrationswere similar in all groups. The mean concentrations of oestradiol,progesterone, testosterone and growth hormone were significantlyhigher (P < 0.01) in follicular fluid with oocytes of intermediatematurity than with mature oocytes (382.5 ng/ml, 7847.5 ng/ml,1704.5 ng/dl and 3.7 ng/ml versus 217.8 ng/ml, 5488.4 ng/ml,1313.6 ng/dl and 2.7 ng/ml, respectively). On the other hand,only oestradiol concentrations were significantly higher infollicular fluid of fertilized compared to non-fertilized oocytes.Concentrations of the other hormones analysed, except growthhormone, were similar in follicular fluid from pregnant andnon-pregnant women after assisted reproduction. Growth hormone,on the other hand, was significantly lower (P < 0.05) infollicular fluid from pregnant compared to non-pregnant women(2.8 versus 3.5 ng/ml). It is concluded that intermediate maturityoocytes and oocytes which will be subsequently fertilized arefound in follicles with higher follicular fluid concentrationsof growth hormone and steroids. Moreover, oocytes leading topregnancy after in-vitro fertilization and embryo transfer arederived from follicles with lower growth hormone concentrationsin follicular fluid.